L-ascorbate (L-ascorbic acid, vitamin C) clearly has an inhibitory effect on cancer cells. However, the mechanism underlying differential sensitivity of cancer cells from same tissue to L-ascorbate is yet to be clarified. Here, we demonstrate that L-ascorbate has a selective killing effect, which is influenced by sodium-dependent vitamin C transporter 2 (SVCT-2) in human breast cancer cells. Treatment of human breast cancer cells with L-ascorbate differentially induced cell death, dependent on the SVCT-2 protein level. Moreover, knockdown of endogenous SVCT-2 via RNA interference in breast cancer cells expressing high levels of the protein induced resistance to L-ascorbate treatment, whereas transfection with SVCT-2 expression plasmids led to enhanced L-ascorbate chemosensitivity. Surprisingly, tumor regression by L-ascorbate administration in mice bearing tumor cell xenograft also corresponded to the SVCT-2 protein level. Interestingly, SVCT-2 expression was absent or weak in normal tissues, but strongly detected in tumor samples obtained from breast cancer patients. In addition, enhanced chemosensitivity to L-ascorbate occurred as a result of caspase-independent autophagy, which was mediated by beclin-1 and LC3 II. In addition, treatment with N-acetyl-L-cysteine, a reactive oxygen species (ROS) scavenger, suppressed the induction of beclin-1 and LC3 II, implying that the differential SVCT-2 protein-dependent L-ascorbate uptake was attributable to intracellular ROS induced by L-ascorbate, subsequently leading to autophagy. These results suggest that functional SVCT-2 sensitizes breast cancer cells to autophagic damage by increasing the L-ascorbate concentration and intracellular ROS production and furthermore, SVCT-2 in breast cancer may act as an indicator for commencing L-ascorbate treatment.
PurposeDiagnosis and proper treatment of renal abscesses remains a challenge for physicians. We investigated the characteristics and comorbidity factors of renal abscesses measuring 5 cm or less and critically examined the effectiveness of conservative treatment.Materials and MethodsBetween February 2001 and March 2009 the records of 63 patients initially diagnosed at our hospital with renal or perirenal abscesses were retrospectively reviewed. In 63 patients with renal and perirenal abscesses, 51 abscesses measured 5 cm or less, and 49 abscesses were treated with intravenous antibiotics alone.ResultsMost patients were women (91.8%), and their mean age was 42.3 years. The mean size of renal abscesses was 3.6 cm. The most common predisposing condition was diabetes mellitus (DM) (46.9%). Common clinical features were fever (83.7%) and flank pain (53.1%). On urinalysis, 31 (64.6%) cases had positive bacterial cultures with Escherichia coli (50.0%) being the most common pathogen. All 49 patients were treated with broad-spectrum intravenous antibiotics alone. All patients showed complete clinical regression and resolution of the renal lesions shown by CT between 3 and 14 weeks. The average hospital stay was 15.3 days (range, 5-31 days). Significant predictors of a long hospital stay were age, abscess size, and DM.ConclusionMedium-sized as well as small-sized renal abscesses were treated successfully with intravenous antibiotics alone. DM was a significant predictor of prolonged hospital stay. If therapeutic drainage is believed to involve considerable risk, then intravenous antimicrobial therapy may be a good alternative treatment.
SummaryWe investigated whether the 2677G>T ⁄ A and 3435C>T polymorphisms of adenosine triphosphate-binding cassette subfamily B member 1 (ABCB1) affect the efficacy of ondansetron to prevent postoperative nausea and vomiting. One hundred and ninety-eight patients undergoing general anaesthesia were enrolled. Thirty minutes before the end of surgery, 0.1 mg.kgondansetron was administered intravenously. The incidence of postoperative nausea and vomiting was compared between genotypes in the 2677G>T ⁄ A and 3435C>T polymorphisms of ABCB1. The incidence of postoperative nausea and vomiting was lower in patients with the 2677TT genotype (TT vs Non-TT = 25.9% vs 53.0%, p = 0.01) and 3435TT genotype (CC + CT vs TT = 52.6% vs 21.7%, p = 0.01) during the first 2 h after surgery. There were no significant differences in the incidence of postoperative nausea and vomiting between the different genotype groupings during period between 2 and 24 h after surgery. In conclusion, ABCB1 genotypes may be a clinical predictor of responsiveness for ondansetron. Postoperative nausea and vomiting (PONV) is a common and distressing complication in patients undergoing general anaesthesia. The incidence ranges between 20% and 30%, but is as high as 80% in high-risk patients [1] and may cause significant complications [2]. Although the exact mechanism of PONV is not clear, it is known that the chemoreceptor trigger zone in the area postrema plays an important role, in which the 5-hydroxytryptamine type-3 (5-HT 3 ) receptor is involved in the occurrence of PONV [3].Currently, 5-HT 3 receptor antagonists such as ondansetron are widely used for prevention and treatment of PONV and although these agents have a significant effect, over 35% of patients treated with ondansetron may still experience PONV [4,5]. We hypothesised that polymorphism in the adenosine triphosphate-binding cassette subfamily B member 1 (ABCB1), an encoding gene of transporter for ondansetron in the brain-blood barrier [6], would contribute to such inter-individual variation.In a previous study, the 3435C>T single nucleotide polymorphism of ABCB1 was associated with the efficacy of 5-HT 3 receptor antagonists for chemotherapy-induced nausea and vomiting [7]. Therefore, we investigated whether the 2677G>T ⁄ A, and 3435C>T polymorphisms of ABCB1 affect the efficacy of ondansetron in preventing PONV in patients undergoing general anaesthesia. MethodsThis study was approved by the Institutional Review Board of Yonsei University Hospital. Written informed consent was obtained from each patient. One hundred and ninety-eight adult patients, of ASA physical status 1-2, undergoing laparoscopic cholecystectomy were enrolled in this study. Patients with a history of drug abuse, known hypersensitivity to 5-HT 3 receptor antagonist, body mass index > 30 kg.m , hepatic or renal disease or who had used antiemetics within the 24 h before the study were excluded. Before surgery, all patients were interviewed about their medical history including tobacco use, presence of PONV and motion sic...
Our study showed that overall incidence of IH was 6.3% after RALP. Nevertheless, RS-RALP carries a lower incidence of IH after surgery, while C-RALP and low BMI are predictors of IH development.
Introduction The adverse effects of long-term drug therapy for prostate cancer (PCa) can dramatically impact patient quality of life and are considered to be important factors when selecting treatment. Aim To assess stretched penile length before and after long-term androgen deprivation therapy (ADT) for treatment of PCa. Methods From January 2008 to June 2010 at a single institution, 39 consecutive patients without distant metastases who were elected to receive ADT as initial therapy for PCa were prospectively enrolled. Exclusion criteria were history of penile anomalies and/or trauma, and prior radical prostate surgery or radiation therapy. Erectile functions were evaluated at baseline according to the International Index of Erectile Function (IIEF). Vertically stretched penile length was measured every 3 months from the pubopenile junction to the meatus with a spring scale. Main Outcome Measure After ADT, significant 3-month interval changes in stretched penile length were noted for up to 15 months (P < 0.001). The relationship between potency and penile shortening was not significant (P = 0.45). Results The mean patient age was 67.1 years. Before therapy, the mean stretched penile length was 10.76 cm. After 24 months of ADT, mean penile length had decreased to 8.05 cm. However, these changes plateaued after 15 months. Normal erectile function (EF) was reported by 41% of patients before therapy, while 10.5% reported normal EF at the 24-month follow-up. The relationship between potency and penile shortening was not significant. However, patients who preserved their potency tended to experience less penile shortening. Conclusions The administration of luteinizing hormone-releasing hormone (LHRH) agonists induced significant decreases in penile length for only up to 15 months in the absence of the confounding effects of surgery and radiation.
PurposeIn Korea, there was no specific guidelines for the management of benign prostatic hyperplasia (BPH). We reviewed the practice patterns of Korean urologists in the management of BPH and aimed to describe the need to develop specific guidelines.Materials and MethodsA probability sample was taken from the Korean Urological Association Registry of Physicians, and a structured questionnaire, that explored practice patterns in the management of BPH, was mailed to a random sample of 251 Korean urologists.ResultsFor the initial evaluation of BPH, most urologists routinely performed prostatic specific antigen (PSA) (96.4%), digital rectal exam (94.4%), international prostate symptom score (IPSS) (83.2%) and transrectal ultrasound (79.2%). Symptom assessment (36.4%) followed by transrectal ultrasound of prostate (TRUS) (20.0%) was considered as the most important diagnostic examination affecting the decision about individual treatment options. Almost all urologists (92.2%) chose medical treatment as the first-line treatment option for uncomplicated BPH with moderate symptoms. Of the respondents, 57.2% had prescribed alpha blocker and 41.6% alpha blocker plus 5-alpha reductase inhibitors as the medical treatment option for BPH. The prescription of 5-ARIs was dependent on the size of the prostate and the severity of symptoms.ConclusionThe results of our current survey provide useful insight into variations in the clinical practice of Korean urologists. They also indicate the need to develop further practical guidelines based on solid clinical data and to ensure that these guidelines are widely promoted and accepted by the urological community.
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